RNA oxidation and iron levels in patients with diabetes

Aim: The urinary biomarker for oxidative stress to RNA, 8-oxo-7,8-dihydro-guanosine (8-oxoGuo) is associated with mortality in patients with type 2 diabetes. Iron has also been linked to diabetes. In individuals with untreated hereditary iron overload it has been observed that 8-oxoGuo was higher compared to controls. In the current study, we hypothesized that 8-oxoGuo was associated with diagnosis of diabetes, and that iron confounded this association. Methods: Participants from a general Danish population were included in the study (n=3567). UPLC-MS/MS method was used for 8-oxoGuo (nmol/mmol creatinine) measurement in spot urine. Iron biomarkers included total plasma iron, ferritin, transferrin saturation (TS) and transferrin. Results: 8-oxoGuo was 17% higher in diabetes patients (n=208) compared to non-diabetes controls. Unadjusted logistic regression model showed an odds ratio of diabetes of 1.38 (95% CI: 1.21-1.57, P < 0.0001) per unit increase of 8-oxoGuo. When the model was adjusted for possible confounders the odds ratio was 1.09 (95% CI: 0.94-1.26, P=0.24). When additional adjustment was performed including ferritin, TS, or transferrin, respectively, the OR were 1.14 (95% CI: 0.97-1.33, P=0.09), 1.10 (95% CI: 0.95-1.28, P=0.18), and 1.17 (95% CI: 1.01-1.38, P=0.04). Conclusions: Our study indicates that 8-oxoGuo is higher in diabetes patients. The lack of association between 8-oxoGuo and diabetes in the adjusted model may be due to the cross-sectional design including post-treatment bias. Our data did not show consistent effect of all iron biomarkers in relation to diabetes. Most likely, the iron biomarkers were affected by inflammation thus not reflecting true iron levels.